EXCHANGE 


THE  SYNTHESIS  OF 
DI-ARYL  THIOPHENES,  DI-ARYL 
SELENOPHENES,  AND  RELATED 
COMPOUNDS 


BY 


PILAR  PEREZ  HERRERA,  Pn.G.,  B.S.,  M.A. 


DISSERTATION 


Submitted   in    partial  fulfillment   of   the  requirements 

for  the  degree  of  Doctor  of  Philosophy  in  the  Faculty  of 

Pure  Science  of  Columbia  University 


NEW  YORK  CITY 
1922 


THE  SYNTHESIS  OF 
DI-ARYL  THIOPHENES,  DI-ARYL 
SELENOPHENES,  AND  RELATED 
COMPOUNDS 

BY 
PILAR  PEREZ  HERRERA,  Pn.G.,  B.S.,  M.A. 


DISSERTATION 


Submitted   in    partial  fulfillment   of   the  requirements 

for  the  degree  of  Doctor  of  Philosophy  in  the  Faculty  of 

Pure  Science  of  Columbia  University 


NEW  YORK  CITY 

1922 


&itfg$ClX3 


TO  MY  MOTHER 


ACKNOWLEDGMENT 

It  gives  the  author  great  pleasure  to  express  in  this  place  her  appre- 
ciation and  gratitude  to  Professor  Marston  Taylor  Bogert,  at  whose 
suggestion  the  following  investigation  was  undertaken,  for  his  kindly 
supervision  and  thoughtful  advice. 

P.  P.  HERRERA. 
Organic  Research  Laboratories 
Havemeyer  Hall,  Columbia  University, 
July,  1922. 


CONTENTS 

PAGE 

DEDICATION 3 

ACKNOWLEDGMENT 5 

ABSTRACT  OF  THE  DISSERTATION >  . . . .  9 

GENERAL  INTRODUCTION 12 

PART  I — DI-ARYL  THIOPHENES 13 

Historical  Review  of  Previous  Work 13 

General  Discussion 14 

Experimental  Part 15 

1.  Preparation  of  Aniline  Zinc  Chloride 15 

2.  Preparation  of  Acetophenon-Anil 15 

3.  Para  Toluidine  Zinc  Chloride 15 

4.  Ortho  Toluidine  Zinc  Chloride 15 

5.  Acetophenon-p-Tolil 15 

6.  Acetophenon-o-Tolil 16 

7.  2,4-Diphenyl  Thiophene 16 

(a)  From  Acetophenon-Anil 16 

(b)  From  Acetophenon-o-Tolil 17 

(c)  From  Acetophenon-p-Tolil 17 

8.  5-HgCl-2,4-Diphenyl  Thiophene 18 

9.  Nitration  of  2,4-Diphenyl  Thiophene 18 

PART  II — DI-ARYL  SELENOPHENES 21 

Historical  Part 21 

Discussion 21 

Experimental  Part 21 

1.  2,4-Diphenyl  Selenophene 21 

(a)  From  Acetophenon-Anil 21 

(b)  From  Acetophenon-p-Tolil 22 

(c)  From  Acetophenon-o-Tolil 23 

2.  5-HgCl-2,4-Diphenyl  Selenophene 23 

3.  Para  Methyl  Acetophenon-Anil 23 

4.  2,4-Di-p-Tolil  Selenophene 24 

5.  Methyl  Ester  of  Orthoformic  Acid 25 

6.  Ethyl  Ester  of  Orthoformic  Acid 25 

7.  Acetophenone  Dimethyl  Acetale 25 


8  Contents 

8.  Acetophenone  Diethyl  Acetale 25 

9.  An  attempt  to  condense  Acetophenone  Diethyl  Acetale 

with  Benzaldehyde 25 

10.  Chalcone  or  Benzalacetophenone 25 

11.  An  attempt  to  prepare  Acetophenon-Guanidine-Anil. ...  25 

BIBLIOGRAPHY 29 

VITA 31 


ABSTRACT  OF  THE  DISSERTATION 


1.  Purpose  of  the  Research. 

To  make  some  further  contributions  to  the  chemistry  of  organic 
selenium  compounds  and  to  develop  a  satisfactory  method  for  preparing 
di-aryl  thiophenes  and  selenophenes  in  a  pure  state  free  from  isomers. 

2.  What  was  attempted. 

An  attempt  was  made  to  study  the  reaction  of  acetophenon-anil  when 
fused  with  sulphur  or  selenium.  There  are  three  possibilities  which  may 
result  from  such  a  fusion,  the  sulphur  combining  with  the  anil  molecule 
according  to  the  following  equations: 

(a) 

C        -    N 

\/\  ^       N 


CH2— H 


S2— >H2ST  + 


CH2 


ace  tophenon-anil 


/3-phenyl-benzo- 
p-thiazine 


This  compound  was  prepared  by  linger  (i)  *  from  amino  thiophenol 
and  co-brom  acetophenone.  It  crystallizes  in  pale  sulphur  yellow,  double 
refractive  cubes  m.p.  233°. 

(b) 


€  =  N— 

I 

CH2 

.1.  .  . 
H    * 


+S2->  H2S 


C  =  N—  - 


CH 


acetophenon-anil 


V 

S 

3-phenylimino- 
thionaphthene- 
2,3 — dihydride 
*  Figures  in  parentheses  refer  to  bibliography,  p.  29. 


•*»»•**•"»*•*  »   •      •  C  •    •     *     1    *  •  " 

10  The  Synthesis  of  Di-Aryl  Thiophenes 


This  compound  has  never  been  prepared. 

(c)  Aniline  splits  off  and  the  sulphur  combines  with  the  acetophenone 
part  of  the  molecule. 

C,H4C CH 


NC.H,; 
H,: 


H,  -|-  S—  >  2  C.H  JSTH,  +  C JIft  •  C CH 

II         II 
N  •  C.H,:  HC        C 


HC  -  C  •  C,H,  S 

2,  4-diphenyl 
thiophene 

or  the  H»S  present  decomposes  the  acetophenon-anil  first  into  thio- 
acetophenone  which  then  forms  the  diphenyl  thiophene  as  described  by 
Baumann  and  Fromm  (2)  according  to  the  following  equations: 

C«H4C  -  NC«Ht+  H^  -  >  Cja^NHj-K  CeH.CSCH, 

I 

CH,  thio-acetophenone 

acetophenon-anil 

CJLCSCH,  --  >  S  +  C.H.CH  .  CH, 
thio-acetophenone  styrol 

2  CJI*CH  =  CH2  -f  3  S  ->  2  H,S  +  CeH6C  -  CH 

II         II 
styrol  HC       C    C,H6 


S 
_     ^.'  2,  4-diphenyl 

thiophene 
C  JI.CH  =  CH,  +  H,S  -  >  S  -f  C  .H,   C^I. 

styrol  ethyl  benzol 

3.  The  Method  of  Attack. 

Equal  moles  of  acetophenon-anil  and  sulphur  (or  selenium)  were  fused 
at  a  temperature  above  200°  C.  yielding  2,  4-diphenyl  thiophene  (or 
selenophene).  To  prove  that  this  is  not  a  reaction  peculiar  to  aceto- 
phenon-anil, two  things  were  necessary: 

(a)  To  show  that  similar  combinations  of  acetophenone  with  other 


Di-A  ryl  Selenophenes,  and  Related  Compounds  1 1 

primary  aromatic  amines,  like  the  toluidines  for  example,  will  give  the 
same  reaction. 

(b)  That  a  homologue  of  acetophenone  like  para  methyl  acetophenone 
may  be  substituted  for  acetophenone  itself. 

4.  In  how  far  were  the  attempts  successful. 

(a)  The  fusion  of  acetophenon-anil,  acetophenon-o-tolil  and  aceto- 
phenon-p-tolil  with  sulphur  (or  selenium)  gave  the  same  compound,  that 
is,  2,4-diphenyl  thiophene  (or  selenophene),  the  difference  being  as  fol- 
lows: in  the  case  of  the  anil,  aniline  was  the  by-product  while  in  the  case 
of  the  tolils,  toluidine  was  the  by-product. 

(b)  Para  methyl  acetophenon-anil  when  fused  with  metallic  selenium 
gave  2,4-di-p-tolil  selenophene. 

5.  What  contribution  actually  new  to  the  science  of  chemistry  has  been  made. 

(a)  A  resume  of  previous  work  on  the  selenophenes  and  di-aryl  thio- 
phenes  has  been  given. 

(b)  A  general  method  for  the  preparation  of  2,4-di-aryl  thiophenes 
and  selenophenes  free  from  isomers  and  in  good  yield  is  given. 

(c)  The  following  new  compounds  have  been  prepared: 

Acetophenon-o-Tolil 
2,4-Diphenyl  Thiophene  * 
5-HgCl-2,4-Diphenyl  Thiophene 
2,4-Diphenyl  Selenophene 
5-HgCl- 2,4-Diphenyl  Selenophene 
Para  Methyl  Acetophenon-Anil 
2,4-Di-p-Tolil  Selenophene 
Acetophenon-Dimethyl  Acetale  * 

*  Not  a  new  compound  but  prepared  by  a  different  method. 


GENERAL  INTRODUCTION 


The  plan  adopted  for  numbering  the  positions  on  the  thiophene  and 
selenophene  nuclei  is  indicated  in  Formulas  I  and  II  so  that  S  or  Se 
is  always  in  position  (I).  This  is  in  agreement  with  the  system  adopted 
in  the  new  (2nd)  edition  of  Meyer- Jacobson's  "  Lehrbuch  der  Organischen 
Chemie."  (3) 


(4) 


(5) 


(3)       (4) 


or 


(»)    (s) 


S  Se 

(i)  d) 

I 


(3)  on 


(a)    (a') 


03'; 


or 

(a)      (a') 

S  Se 

II 


(a) 


Although  acetophenon-anil  has  served  as  a  starting  material  through- 
out this  work,  the  problems  involved  are  essentially  different  and  there- 
fore it  was  deemed  advisable  to  present  the  subject  in  two  parts: 

I.  Di-Aryl  Thiophenes. 

II.  Di-Aryl  Selenophenes. 


PART  I 
DI-ARYL  THIOPHENES 

In  1888  Kopf  and  Paal  (4)  in  connection  with  some  work  on  phenacyl- 
benzoyl  acetic  ether,  obtained  from  diphenacyl  and  phosphorous  penta- 

/C(C,H6)  =  CH 
sulphide  at  i6o°-i8o°  a,  a'-diphenyl  thiophene,  S\^  |     white 

XC(C6H6)  =  CH 

shiny  flakes  melting  at  i52°-i53°.    The  yield  is  approximately  60-70% 
of  the  theory. 

In  1895  Baumann  and  Fromm  (5)  by  heating  cinnamic  acid  with 
sulphur  at  240°  obtained  a  mixture  of  2,4-diphenyl  thiophene  m.p. 
H9°-i2o°  and  2,5-diphenyl  thiophene  m.p.  152°-! 53°;  and  by  heating 
styrol  with  sulphur  at  230°  they  obtained  a  mixture  of  ethyl  benzol  b.p. 
I33°~I34°>  2,4-diphenyl  thiophene  m.p.  119°,  and  2,5-diphenyl  thiophene 
m.p.  i52°-i53°.  The  same  authors  (6)  found  that  by  distilling  trithio- 
acetophenone  they  obtained  ethyl  benzol  and  a  mixture  of  2,4-  and  2,5- 
diphenyl  thiophenes.  The  fact  that  when  anhydrotriacetophenon  disul- 
phide  (7)  is  heated  it  yields  2,4-diphenyl  thiophene  together  with  some 
styrol  and  hydrogen  sulphide  according  to  the  following  reaction, 


>H2S+C8H8+S<V  I 

S  -  C  =     CH  styrol  XC(C6H6)  =  CH 

2,4-diphenyl 

C6H6  thiophene 

anhydro-triacetophenon 
disulphide 

proves  the  constitution  of  2,4-diphenyl  thiophene.  No  2,5-diphenyl 
thiophene  was  formed.  Baumann  and  Fromm  (8)  also  found  that  when 
acetophenone  in  alcoholic  solution  is  saturated  with  hydrogen  sulphide  in 
the  presence  of  ammonia  and  allowed  to  stand  for  14  days  they  obtained 
besides  ethyl  benzol  and  styrol,  a  mixture  of  2,4-  and  2,5-diphenyl 


14  The  Synthesis  of  Di-Aryl  Thiophenes 

thiophenes  and  free  sulphur.  The  yield  of  2,4-diphenyl  thiophene  ob- 
tained is  i%  of  the  theory. 

In  1909  Willgerodt  and  Merk  (9)  obtained  by  heating  in  a  tube  at 
210°,  3  g.  of  acetophenone,  3  cc.  of  water  and  5  g.  of  solid  colorless  am- 
monium sulphide,  phenyl  acetamide,  phenyl  acetic  acid,  ethyl  benzol, 
2,4-diphenyl  thiophene  m.p.  124°  and  2,$-diphenyl  thiophene  m.p.  150.5°. 

It  is  apparent  therefore,  that  although  the  di-aryl  thiophenes  have 
been  prepared  before,  yet  up  to  the  present,  no  entirely  satisfactory 
method  has  been  developed  for  preparing  them  in  a  pure  state.  Hereto- 
fore, there  always  resulted  a  mixture  of  the  two  isomers  and  the  yield 
obtained  was  very  small. 

We  have  found,  however,  that  by  fusing  acetophenon-anil  with  sulphur 
at  a  temperature  of  220°  to  240°  C.,  we  get  a  very  satisfactory  yield  of 
2,4-diphenyl  thiophene  m.p.  124°  C.  (u.c.)  or  122.5°  (cor.),  inasmuch  as 
no  isomers  or  other  compounds  such  as  styrol  and  ethyl  benzol  are  formed, 
the  amount  of  pure  product  obtained  being  28%  of  the  theory.  The 
compound  is  identical  with  Baumann  and  Fromm's  (10)  2,4-diphenyl 
thiophene  melting  at  119°-!  20°.  This  method  proves  to  be  generally 
applicable  for  the  preparation  of  2,4-di-aryl  thiophenes  and  selenophenes. 


EXPERIMENTAL  PART 


1.  ANILINE  ZINC  CHLORIDE,  (C6H6NH2)2 .  ZnCl2. 

This  compound  was  made  following  the  directions  of  Lachowicz  and 
Bandrowski  (i i).  It  was  found  necessary  to  add  just  enough  HC1  to  the 
aqueous  solution  of  zinc  chloride  to  get  it  in  solution. 

2.  ACETOPHENON-ANIL,  C^C  ^5,' 

N   IM^ells 

This  compound  was  prepared  according  to  Reddelien's  (12)  method. 
The  reaction  proceeds  as  described  and  the  yield,  melting  point,  and 
boiling  point  coincide  with  those  given. 

Bogert's  (13)  apparatus  was  used  to  separate  all  the  unchanged  aceto- 
phenone  from  the  anil. 

3.  PARA  TOLUIDINE  ZINC  CHLORIDE,  (p)  (C6H4<^™3)2 .  ZnCl2 

This  compound  was  prepared  by  adding  to  a  solution  of  13.6  g.  (o.i 
mole)  of  ZnCl2  in  100  cc.  of  95%  alcohol  a  solution  of  21.4  g  (0.2  mole)  of 
(p)  toluidine  in  100  cc.  of  95%  alcohol. 

Fine  white  needles.    Yield,  32  g.  or  91.4%  of  the  theory. 

4.  ORTHO  TOLUIDINE  ZINC  CHLORIDE,  (o)  (C6H4<(™3)2 .  ZnCl2 

Prepared  in  the  same  way  as  (p)  toluidine  zinc  chloride. 
White  fine  needles.    Yield,  31  g  or  88.6%  of  the  theory. 


5.  ACETOPHENON-P-TOLIL, 


N\/\ 


CH3 


\/ 


-CH3 


Prepared  according  to  Reddelien's  method  (14).  Light  yellow  oil,  not 
very  viscous,  which  when  exposed  to  the  air  soon  turns  brown.  Yield, 
33-7%  of  the  theory. 


i6 


The  Synthesis  of  Di-Aryl  Thiophenes 


CH, 


6.  ACETOPHENON-O-TOLIL, 


— C  =  N— 


CH, 


x\ 


\x 


Mix  380  g.  of  acetophenone,  475  g.  of  (o)  toluidine  and  19  g.  of  (o) 
toluidine  zinc  chloride  in  a  round  bottom  flask  and  heat  in  an  oil  bath 
at  a  temperature  of  1 70°-!  80°  C.  for  i  hour.  Allow  to  cool,  add  chloroform 
to  the  melted  oil  and  filter  off  the  (o)  toluidine  zinc  chloride  salt.  Dis- 
till the  filtrate  up  to  220°  C.  and  the  rest  is  distilled  under  diminished 
pressure.  The  main  portion  distilling  at  2io°-220°  €.,57  mm.  pressure 
is  a  light  yellow  oil  which  does  not  solidify.  Yield,  323  g  or  48.8%  of 
the  theory. 

Light  yellow  oil  not  very  viscous,  which  when  exposed  to  the  air 
soon  turns  brown. 

7.  2,4-DIPHENYL  THIOPHENE,  C«H6C CH 

II          II 
HC         C .  C.H8 

\> 

S 

(a)  From  Acetophenon-Anil. 

A  mixture  of  60  g.  of  acetophenon-anil  (0.3  mole)  and  20  g.  of  powdered 
roll  sulphur  (0.3  mole)  was  placed  in  a  distilling  flask  provided  with  an 
air  condenser  and  kept  at  a  temperature  of  220°  to  240°  C.  for  thirteen 
hours.  Aniline  distilled  off  and  some  H2S  was  evolved.  The  melt  was 
distilled  under  diminished  pressure.  The  main  portion  distilling  at  260°- 
265°  C.,  36  mm.  pressure,  was  a  yellow  oil  which  solidified  in  the  receiver 
to  a  yellow  crystalline  mass.  The  solid  distillate  was  recrystallized  from 
absolute  alcohol  to  constant  melting  point  a  little  norite  being  added  to 
the  alcoholic  solution.  Absolute  purity  requires  two  or  three  recrystalliza- 
tions  from  absolute  alcohol.  White  shiny  plates,  melting  at  122.5°  C. 
(cor.)  were  obtained.  Yield,  10  g.  or  28%  of  the  theory. 

Easily  soluble  in  chloroform,  ether,  and  acetone;  soluble  in  hot  petro- 
leum ether,  benzol,  alcohol,  and  glacial  acetic  acid;  insoluble  in  water, 
HC1,  and  alkali.  It  gives  a  yellow  color  with  concentrated  H2SO< 
and  a  red  color  with  concentrated  nitric  acid.  It  does  not  form  an 


Di-Aryl  Selenophenes,  and  Related  Compounds  if 

addition  product  with  methyl  iodide.  With  concentrated  sulphuric 
acid  and  isatin  (Indophenin  Test  [15] )  a  bluish  green  dye  is  precipitated. 
With  Laubenheimer's  Test  (16),  a  green  dye  is  precipitated,  which  is 
soluble  in  ether,  alcohol,  benzol,  and  glacial  acetic  acid  with  cherry  red 
coloration.  With  nitrososulphuric  acid  (Liebermann's  Reaction  [17] ) 
we  get  a  green  then  dark  red  coloration  of  the  sulphuric  acid. 

Qualitative  analysis  showed  the  presence  of  C,  H,  and  S  but  no  nitro- 
gen. 

It  was  analyzed  for  C  and  H  by  Fisher's  (18)  method  and  for  S  by 
Carius'  (19)  method. 

Analysis : 

Calculated  for  C16H12S:    C  =  81.3%,  H  =  5.08%,  S  =  13.54% 

Found  T       1  8l'I9%'  H       !  4'89%'  S          I3'6?% 

F°Und  C  =  [  81.03%  H  =  I  4-88%  S  -  |  I3.8o% 

No  styrol,  ethyl  benzol,  or  isomeric  2,5-diphenyl  thiophene  were  en- 
countered. 

(b)  From  Acetophenon-o-Tolil. 

A  mixture  of  149  g.  of  acetophenon-o-tolil  and  46  g.  of  powdered 
sulphur  roll  was  placed  in  a  distilling  flask  provided  with  an  air  con- 
denser and  heated  in  an  oil  bath  at  a  temperature  of  24o°-25o°  C.  for 
19  hours.  The  reaction  started  at  240°  C.  30  g.  of  (o)  toluidine  distilled 
off  during  the  heating.  When  heated  with  acetic  anhydride,  (o)  acet- 
toluide(2o),  CH3C6H4NHCOCH3,  white  needles  m.p.  110°  C.  was 
obtained. 

The  melt  was  distilled  under  diminished  pressure.  The  main  portion 
distilling  at  26o°-265°  C.,  36  mm.  pressure  was  a  yellow  oil  which  solidi- 
fied in  the  receiver  to  a  yellow  crystalline  mass.  The  solid  distillate 
was  recrystallized  from  absolute  alcohol  to  constant  melting  point  a 
little  norite  being  added  to  the  alcoholic  solution. 

White  shiny  plates,  m.p.  122.5°  C.  (cor.).  Yield,  20  g.  or  23.6%  of 
the  theory.  It  has  the  same  crystalline  structure  and  the  same  melting 
point  as  the  2,4-diphenyl  thiophene  obtained  from  acetophenon-anil. 
A  mixture  of  the  two  compounds  gave  a  melting  point  of  122.5°  C-  (cor.). 

(c)  From  Acetophenon-p-Tolil. 

92  g.  of  acetophenon-p-tolil  and  28.4  g.  of  powdered  sulphur  roll  were 
placed  in  a  distilling  flask  provided  with  an  air  condenser  and  heated 
in  an  oil  bath  at  a  temperature  of  230^250°  C.  for  19  hours.  The  re- 
action started  at  230°  C.  10  g.  of  (p)  toluidine  were  recovered  during  the 
heating.  When  tested  with  acetic  anhydride,  (p)  acettoluide  (21) 


i8  The  Synthesis  of  Di-Aryl  Thiophenes 

CHaCJIiNHCOCH,,  lustrous  white  needles  m.p.  148.3°  C.  (cor.)  were 
obtained. 

The  rest  is  the  same  as  with  acetophenon-o-tolil. 

White  shiny  plates  m.p.  122.5°  C.  (cor.).  Yield,  17  g.  or  32.4%  of 
the  theory. 

It  has  the  same  melting  point  and  the  same  crystalline  structure  as 
2,4-diphenyl  thiophene  and  a  mixture  of  the  two  compounds  gave  a 
melting  point  of  122.5°  C.  (cor.). 

8.  5-HgCl-2,4-DIPHENYL  THIOPHENE,  CJI,  •  C CH 

II          II 
HgCl   C         C    C«H* 


S 

Steinkopf  and  Bauermeister  (22)  prepared  HgCl-2-phenyl  thiophene 
from  2-phenyl  thiophene  and  mercuric  chloride.  The  analogous  reaction 
was  attempted  in  the  case  of  2,4-diphenyl  thiophene. 

To  a  solution  of  i  g.  of  2,4-diphenyl  thiophene  in  200  cc.  of  95%  al- 
cohol add  10  g.  of  a  33%  solution  of  sodium  acetate  and  50  g.  of  a  cold 
saturated  solution  of  mercuric  chloride.  Mix  well  and  allow  to  stand. 
After  two  and  a  half  days,  1.5  g.  of  5-HgCl- 2,4-diphenyl  thiophene  in 
the  form  of  white  needles  were  obtained.  After  four  days  more,  0.5  g. 
more  were  obtained.  The  product  was  recrystallized  from  hot  alcohol 
in  which  it  is  difficultly  soluble,  to  constant  melting  point.  White  silky 
needles  m.p.  223°  C.  (cor.).  Yield,  1.5  g.  or  75%  of  the  theory. 

Easily  soluble  in  hot  chloroform  and  benzol,  difficultly  soluble  in  hot 
alcohol  and  glacial  acetic  acid,  insoluble  in  ether.  It  gave  a  qualitative 
test  for  sulphur. 

Calculated  for  C,JHnSHgCl:  Hg  =  42.57% 

Found  Hg  -  43-93% 

9.  NITRATION  OF  2,4-DIPHENYL  THIOPHENE. 

In  a  round  bottom  flask  provided  with  a  3-hole  stopper  one  hole  con- 
taining a  dropping  funnel,  another  a  tube  connected  to  the  water  pump, 
and  the  third  a  capillary  tube,  place  5  g.  of  2,4-diphenyl  thiophene  and 
50  cc.  of  acetic  anhydride.  In  the  dropping  funnel  place  1.5  cc.  of  fuming 
nitric  acid  (sp.  gr.  1.5)  and  1.5  cc.  of  acetic  anhydride.  Immerse  the 
flask  in  a  freezing  mixture  in  order  to  keep  the  temperature  at  o-5°C. 
and  very  slowly,  drop  by  drop,  add  the  nitrating  mixture  at  the  same 


Di-Aryl  Selenophenes,  and  Related  Compounds  19 

time  drawing  air  into  the  flask.  The  reaction  mixture  turns  brown. 
After  all  the  nitrating  mixture  has  been  added,  keep  the  flask  in  the 
freezing  mixture  for  5  minutes  longer  then  pour  the  reaction  product 
into  ice  water,  stir  thoroughly,  and  allow  to  cool. 

A  reddish  oil  which  soon  solidifies  to  a  reddish  brown  crystalline  mass 
is  obtained.  It  does  not  distill  with  steam.  It  was  filtered  off,  dried, 
and  powdered.  It  is  insoluble  in  water,  alkali,  petroleum  ether,  ethyl 
alcohol  and  methyl  alcohol.  Easily  soluble  in  ether,  chloroform,  benzol, 
acetone,  toluene  and  ethyl  acetate  but  does  not  crystallize  from  any  of 
these  solvents.  Soluble  in  hot  glacial  acetic  acid.  At  8o°-85°  C.,  it 
begins  to  decompose  and  at  iio°-ii5°  C.  it  forms  a  brown  liquid.  When 
pulverized  it  forms  a  yellowish  brown  powder. 

The  product  obtained  was  not  pure  enough  for  combustion. 


PART  II 
DI-ARYL  SELENOPHENES 

Up  to  the  present,  very  little  work  has  been  done  on  selenophene  com- 
pounds. The  first  compound  of  this  class  was  prepared  by  Paal  (23)  in 
1885.  By  heating  ace  tony  lace  tone  with  phosphorous  pentaselenide  at 
180°,  he  obtained  selenoxene  or  2,5-dimethyl  selenophene. 

In  1894,  Zoppellari  (24),  in  connection  with  his  work  on  "Atomic  Re- 
fraction of  Selenium,"  determined  the  vapor  density  and  the  percentage 
of  carbon  and  hydrogen  in  selenoxene. 

In  1909,  Foa  (25)  prepared  selenophene  itself  by  heating  in  a  com- 
bustion tube  52.9  g.  of  sodium  succinate  and  100  g.  of  phosphorous 
triselenide.  He  obtained  a  yellowish  liquid  boiling  at  i47°-i49°,  250  mm. 
pressure.  The  yield  was  very  small. 

Our  method  for  the  synthesis  of  2,4-diphenyl  thiophene  having  proved 
successful  and  in  view  of  the  fact  that  selenium  reacts  very  similar  to 
sulphur,  it  was  decided  to  apply  the  same  method  for  the  preparation 
of  di-aryl  selenophenes.  A  good  yield  of  2,4-diphenyl  selenophene  melt- 
ing at  112.3°  C.  (cor.)  was  obtained  by  fusing  acetophenon-anil  and 
metallic  selenium  at  a  temperature  of  280°  to  295°  C. 

It  will  be  noted  that  as  far  as  possible  we  endeavored  to  duplicate 
our  sulphur  compounds  with  selenium  compounds  and  in  every  instance 
obtained  the  desired  results. 

EXPERIMENTAL  PART 

i.  2,4-DI-PHENYL  SELENOPHENE,  C6H5   C CH 

II          II 
HC         C  •  C6H5 

\/ 

Se 

(a)  From  Acetophenon-Anil. 

A  mixture  of  60  g.  of  acetophenon-anil  (0.3  mole)  and  48.6  g.  of  metallic 
selenium  (0.3  mole)  was  placed  in  a  distilling  flask  provided  with  an  air 
condenser  and  heated  in  a  KNO3  bath  at  a  temperature  of  280°  to  295°  C. 
for  1 6  hours.  The  reaction  started  at  280°  C.,  at  which  temperature 
aniline  distilled  off.  About  30  cc.  of  aniline  were  obtained.  When  treated 
with  acetic  anhydride  we  obtained  acetanilide  (26)  m.p.  112.7°  C.  (cor.). 


22  The  Synthesis  of  Di-Aryl  Thiophenes 

The  melt,  a  solid  crystalline  mass,  was  distilled  under  diminished 
pressure.  The  main  portion  distilled  at  270°  to  280°  €.,31  mm.  pres- 
sure, and  was  a  reddish  oil  which  solidified  in  the  receiver.  It  was  re- 
crystallized  from  absolute  alcohol  to  constant  melting  point  a  little 
norite  being  used.  Shiny  colorless  scales  m.p.  112.3°  C.  (cor.).  Yield, 
J3  g-  °r  3°%  of  the  theory. 

Easily  soluble  in  chloroform,  ether,  benzol,  and  acetone;  soluble  in 
hot  alcohol  and  glacial  acetic  acid;  insoluble  in  water,  NaOH  solution 
and  HCL. 

With  concentrated  HNOi  it  gives  a  dark  red  coloration,  and  is  oxi- 
dized. It  dissolves  in  concentrated  H^O4  with  an  orange-yellow  colora- 
tion. With  isatin  and  cone.  H,SO4  (Indophenin  Test  [27] )  it  gives  a 
brown  color.  By  adding  water  the  dye  is  precipitated  as  a  brown  mass. 
With  Laubenheimer's  Test  (28)  it  gives  a  green  color.  On  adding  water 
the  dye  is  precipitated  in  the  form  of  green  flocks  soluble  in  ether,  al- 
cohol, and  glacial  acetic  acid  with  orange-yellow  color;  in  benzol,  with 
deep  orange  color;  in  cone.  HjSO4,  with  violet  red  color.  With  Lieber- 
mann's  Test  (29),  it  gives  a  green  then  a  brownish  black  color. 

Qualitative  analysis  showed  the  presence  of  C,  H,  and  Se. 

Analysis: 

Calculated  for  C,,H,,Se:  C  -  67.77%,  H  «  4.27% 

Found  C  -  67.74%,  H  -  4-30% 

(b)  From  Acetophenon-p-Tolil. 

A  mixture  of  125  g.  of  acetophenon-p-tolil  (0.6  mole)  and  95.4  g.  of 
metallic  selenium  (0.6  mole)  was  placed  in  a  distilling  flask  provided 
with  an  air  condenser  and  heated  in  a  KNOi  bath  at  a  temperature  of 
27o°-290°  C.  for  23  hours.  About  50  g.  of  (p)  toluidine  was  recovered. 
When  heated  with  ace  tic  anhydride  it  gave  (p)  acettoluide  (30),  CH,CeH4- 
NHCOCH,,  lustrous  white  needles  m.p.  148.3°  C.  (cor.). 

The  melt  was  distilled  under  diminished  pressure.  The  main  portion 
distilled  at  27o°-28o°C.,  31  mm.  pressure  and  was  a  reddish  oil  which 
solidified  in  the  receiver  to  a  reddish  crystalline  mass.  It  was  recrystal- 
lized  from  absolute  alcohol  to  constant  melting  point,  a  little  norite 
being  added. 

Shiny  colorless  scales  m.p.  112.3°  C.  (cor.).  Yield,  25  g.  or  29.3%  of 
the  theory. 

It  has  the  same  crystalline  structure  and  the  same  melting  point  as 
2,4-diphenyl  selenophene  and  a  mixture  of  the  two  compounds  gave  a 
melting  point  of  112.3°  C.  (cor.). 


Di-Aryl  Selenophenes,  and  Related  Compounds  23 

(c)  From  Acetophenon-o-Tolil. 

173  g.  of  acetophenon-o-tolil  and  132  g.  of  metallic  selenium  powder 
were  placed  in  a  distilling  flask  provided  with  an  air  condenser  and  heated 
in  a  KNO3  bath  at  a  temperature  of  2'jo°-2go°  C.  for  23  hours.  79  g.  of 
(o)  toluidine  were  recovered  during  the  heating.  When  tested  with 
acetic  anhydride  it  gave  (o)  acettoluide  (31),  CHjC^NHCOCH,,  color- 
less needles  m.p.  1 10°  C. 

The  rest  is  the  same  as  with  acetophenon-p-tolil. 

Colorless  shiny  scales  m.p.  ii2.3°C.  (cor.).  Yield,  27  g.  or  23%  of 
the  theory. 

It  has  the  same  melting  point  and  the  same  crystalline  structure  as 
2,4-diphenyl  selenophene.  A  mixture  of  the  two  compounds  gave  a 
melting  point  of  112.3°  C.  (cor.). 

2.  5-HgCl-2,4-DIPHENYL  SELENOPHENE,  C«H6  •  C C  -  H 

II          II 
HgCl   C         C    C&6 

\/ 
Se 

To  a  solution  of  5  g.  of  2 ,4-diphenyl  selenophene  in  i  li ter  of  95%  alcohol, 
add  50  g.  of  a  33%  solution  of  sodium  acetate  and  250  g.  of  a  cold  satu- 
rated solution  of  mercuric  chloride.  Shake  well  and  allow  to  stand. 
After  20  hours,  8  g.  of  5-HgCl- 2,4-diphenyl  selenophene  were  obtained 
in  the  form  of  colorless  fine  needles.  After  24  hours  more,  2  g.  were 
obtained  and  after  three  and  a  half  days,  i  g.  more.  It  was  recrystallized 
from  95%  alcohol  to  constant  melting  point.  Fine  needles  m.p.  224°C. 
(cor.).  Yield,  8  g.  or  89%  of  the  theory. 

Easily  soluble  in  hot  CHC13,  benzol,  and  glacial  acetic  acid.  Diffi- 
cultly soluble  in  alcohol  and  ether.  Insoluble  in  water. 

Qualitative  analysis  showed  the  presence  of  Se  and  Hg. 

A  mixture  of  equal  parts  of  CieHuSe.HgCl  m.p.  224°  C.  (cor.)  and 
CieHuS.HgCl  m.p.  223°  C.  (cor.)  gave  a  melting  point  of  219°  C.  (cor.). 

3.  PARA  METHYL  ACETOPHENON-ANIL, 


CH3/ 


24  The  Synthesis  of  Di-Aryl  Thiophenes 

100  g.  of  (p)  methyl  acetophenone  and  125  g.  of  aniline  (redistilled) 
were  placed  in  a  round  bottom  flask  and  heated  in  an  oil  bath  to  160°  C. 
then  5  g.  of  aniline  zinc  chloride  was  added  and  the  temperature  raised 
to  1 80°  for  i  hour.  The  melted  oil  was  allowed  to  cool,  chloroform  was 
added  and  the  aniline  zinc  chloride  salt  filtered  off.  The  filtrate  was 
distilled  up  to  200°  C.  and  the  remaining  portion  was  distilled  under 
diminished  pressure.  The  main  portion  distilled  at  22o°-24o°  C.,  53 
mm.  pressure.  Yield,  46  g.  or  29.5%  of  the  theory. 

Light  yellow  oil  not  very  viscous  which  when  exposed  to  the  air  soon 
turns  brown. 

4.  2,4-DI-P-TOLIL  SELENOPHENE,  CH,CeH4   C CH 

II         II 
HC        C  •  C6H4CHS 


Se 

A  mixture  of  46  g.  of  (p)  methyl  acetophenon-anil  (0.22  mole)  and 
35  g.  of  metallic  selenium  (0.22  mole)  was  placed  in  a  distilling  flask 
provided  with  an  air  condenser  and  heated  in  a  KNO»  bath  at  a  tem- 
perature of  26o°-27o°  C.  for  n  hours.  The  reaction  started  at  260°  C. 
13  g.  of  aniline  distilled  off  during  the  heating.  When  tested  with  acetic 
anhydride  it  gave  acetanilide  (32),  white  leaflets  m.p.  112.7°  C.  (cor.). 

The  melt,  a  solid  mass,  was  distilled  under  diminished  pressure.  The 
main  portion  distilled  at  26o°-28o°  C.,  38  mm.  pressure  and  was  a  red- 
dish oil  which  solidified  in  the  receiver.  It  was  recrystallized  from  ab- 
solute alcohol  to  constant  melting  point  a  little  norite  being  added  to 
the  alcoholic  solution. 

Beautiful  colorless  shiny  leaflets  m.p.  136.3°  C.  (cor.).  Yield,  7  g. 
or  20.5%  of  the  theory. 

Easily  soluble  in  CHC18,  ether,  benzol,  and  acetone;  soluble  in  hot 
alcohol  and  glacial  acetic  acid;  insoluble  in  water,  NaOH  solution  and 
HC1.  It  dissolves  in  cone.  H2SO4  with  red  coloration.  It  is  oxidized  by 
cone.  HNO3.  With  isatin  and  cone.  H2SO4  (Indophenin  Test  [33])  it 
gives  a  bright  red  coloration.  With  Laubenheimer's  Test  (34)  a  green 
dye  is  precipitated.  The  dye  is  soluble  in  ether  with  orange  yellow 
coloration;  in  alcohol,  benzol  and  glacial  acetic  acid  with  orange  color; 
in  cone.  H2SO4  with  brown  coloration.  On  addition  of  H2O  to  the  H2SO4 
solution,  the  green  dye  is  reprecipitated.  With  Liebermann's  Test  (35) 
it  gives  a  dark  green  coloration  of  the  H2SO4. 


Di-Aryl  Selenophenes,  and  Related  Compounds  25 

Qualitative  analysis  showed  the  presence  of  C,  H,  and  Se  but  no  N. 

Analysis: 

Calculated  for  C18H16Se:  C  =  69.45%;  H  =  5.14% 

Found  C  =  69.40%;  H  =  5.39% 

5.  METHYL  ESTER  OF  ORTHOFORMIC  ACID,  HC(OCH3)3. 

72  g.  of  finely  cut  metallic  sodium  are  mixed  with  600  cc.  of  absolute 
ether  and  to  this  add  slowly,  while  cooling  with  ice,  100  cc.  of  absolute 
methyl  alcohol.  Stopper  the  flask  with  a  CaCl2  tube  and  allow  to  stand 
for  one  day.  Cool  with  ice,  carefully  add  86.6  g.  of  chloroform  and 
then  heat  for  a  time  in  a  flask  provided  with  a  reflux  condenser.  Filter 
off  the  NaCl  formed,  evaporate  the  ether  on  a  water  bath,  and  distil 
the  rest  under  diminished  pressure.  The  main  portion  distills  at  45°  C., 
65  mm.  pressure. 

A  pleasant  smelling  liquid,  slightly  soluble  in  water,  and  inflammable. 
Yield,  22.2  g.  or  28%  of  the  theory. 

6.  ETHYL  ESTER  OF  ORTHOFORMIC  ACID,  HC(OC2H6)3. 

Prepared  according  to  Bender  and  Erdmann  (36). 

OCH3 

1 

7.  ACETOPHENONE  DIMETHYL  ACETALE,  CeH6— C CH3 

OCH3 

Mix  22  g.  of  methyl  ester  of  orthoformic  acid,  16.2  g.  of  acetophenone 
and  18.9  g.  of  absolute  methyl  alcohol  with  5  drops  of  cone.  HC1  in  a 
flask  fitted  with  a  CaCl2  tube  and  heat  the  mixture  to  40°  C.  with  fre- 
quent shaking.  The  odor  of  acetophenone  disappears  and  is  replaced 
by  the  pleasant  flowery  odor  of  the  acetale.  Allow  to  stand  for  16  hours. 
Make  the  mixture  alkaline  with  a  drop  of  alcoholic  sodium  methylate, 
distill  the  alcohol  and  the  residue  is  distilled  under  diminished  pressure. 
The  main  portion  distills  at  90°  C.,  20  mm.  pressure.  Yield,  20  g.  or 
89.3%  of  the  theory. 

Colorless  liquid  with  flowery  odor. 

8.  ACETOPHENONE  DIETHYL  ACETALE,  C«H6C(OC2H5)2CH3 
Prepared  according  to  Claisen  (37). 

9.  AN  ATTEMPT  TO  CONDENSE  ACETOPHENONE  DIETHYL 

ACETALE  WITH  BENZALDEHYDE. 

An  attempt  was  made  to  condense  acetophenone  diethyl  acetale  with 


26  The  Synthesis  of  Di-Aryl  Thiophenes 

benzaldehyde  with  a  view  of  getting  a  substituted  chalcone  according  to 
the  following  equation: 

C«H5C(OC,H»),CH  —  |H7+O"|—  HCC«H5  —  >  H2O  + 

c8H6c(oc,H4)2CH=  CHC.HS 

(a)  3  g.  of  acetophenone  diethyl  acetale,  1.6  g.  of  benzaldehyde  (re- 
distilled) and  0.5  g.  of  a  20%  sodium  ethylate  solution  were  mixed  in  a 
corked  flask  and  allowed  to  stand  for  a  day  in  a  freezing  mixture.    A 
light  yellow  gelatinous  mass  was  obtained. 

Soluble  in  hot  95%  alcohol;  insoluble  in  ether,  CHCU,  petroleum  ether 
and  anhydrous  ethyl  acetate.  Heated  in  a  dry  test  tube  it  forms  an 
oil.  Easily  hydrolized  with  water.  It  could  not  be  crystallized.  It 
behaves  very  much  like  chalcone. 

(b)  2  g.  of  acetophenone  diethyl  acetale,  i  g.  of  benzaldehyde  (re- 
distilled) and  i  cc.  of  10%  sodium  ethylate  solution  were  mixed  and 
heated  under  pressure  between  ioo°-io5°  C.  for  i  hour.    A  solid  yellow- 
ish mass  was  obtained.    It  was  washed  with  ether  and  dried  in  a  vacuum. 
It  had  the  same  properties  as  (a). 

(c)  2  g.  of  acetophenone  diethyl  acetale,  i  g.  of  benzaldehyde  (redis- 
tilled), 10  g.  of  95%  alcohol  and  i  cc.  of  10%  NaOH  solution  were  mixed 
and  allowed  to  stand  in  a  corked  flask  for  one  day.    No  change  occurred. 
The  mixture  was  poured  into  a  beaker  and  evaporated  in  a  dessicator  under 
reduced  pressure.     A  solid  mass  which  behaved  like  (a)  was  obtained. 

10.  CHALCONE    OR    BENZALACETOPHENONE,    CeH.COCH  . 

CHCJI,. 
Prepared  from  acetophenone  and  benzaldehyde  according  to  Claisen  (38)  . 

1  1  .  AN  ATTEMPT  TO  PREPARE  ACETOPHENON-GUANIDINE- 
ANIL, 


\_NH 


Attempts  were  made  to  prepare  this  compound  from  acetophenone 
and  guanidine  carbonate  as  follows: 


C.H.C  =  10+H.JN       _  ^   HiCO,>H!o+  K.CO.+ 

CH,  ' 


Di-Aryl  Selenophenes,  and  Related  Compounds  27 

(a)  Condensation  with  KOH. 

12  g.  of  acetophenone  were  dissolved  in  just  enough  ethyl  alcohol  and 
mixed  with  a  concentrated  aqueous  solution  of  guanidine  carbonate. 
The  mixture  was  made  strongly  alkaline  with  KOH  solution  and  warmed 
for  2  hours  on  a  water  bath. 

The  method  did  not  work.  Guanidine  carbonate  is  insoluble  in  al- 
cohol. On  addition  of  KOH,  ammonia  is  liberated. 

(b)  Condensation  with  ZnCl2. 

12  g.  of  acetophenone,  22  g.  of  guanidine  carbonate  and  i  g.  of  ZnCl2 
were  mixed  and  heated  at  180°  C.  for  >£  hour.  The  melt  was  extracted 
with  60%  alcohol. 

On  attempting  to  concentrate  the  alcoholic  extract  an  oil  separated. 
This  oil  was  extracted  with  ether  and  distilled.  Acetophenone  was 
recovered. 

The  residue  from  the  ether  extraction  gave  a  solid  mass  on  concen- 
tration. This  was  insoluble  in  alcohol  and  water  but  soluble  in  water 
acidified  with  HC1.  It  proved  to  be  Guanidine. 


BIBLIOGRAPHY 

1.  Unger,  Berichte,  30,  607,  2393  (1897). 

2.  Baumann  and  Fromm,  Berichte,  28,  903  (1895). 

3.  Meyer- Jacobson,   "Lehrbuch  der  Organischen   Chemie,"   Vol.    2, 

Part  3,  p.  no. 

4.  Kopf  and  Paal,  Berichte,  21,  3053,  3058  (1888). 

5.  Baumann  and  Fromm,  Berichte,  28,  891,  893  (1895). 
Baumann  and  Fromm,  Berichte,  30,  in,  117  (1897). 

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9.  Willgerodt  and  Merk,  Jour.  Pr.  Chem.  (2)  80,  193  (1909). 
Willgerodt  and  Merk,  Centralblatt  (1909),  II,  981-2. 
Willgerodt  and  Scholtz,  Centralblatt  (1910),  I,  1969. 

10.  (See  5.) 

n.  Lachowicz  and  Bandrowski,  Monatshefte,  p,  513  (i< 

12.  Reddelien,  Berichte,  43,  2478  (1910). 

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14.  Reddelien,  Annalen,  388,  185  (1912). 
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17.  Victor  Meyer,  Berichte,  16,  1473  (l883)- 


30  The  Synthesis  of  Di-Aryl  Thiophenes 

Liebermann,  Bench te,  20,  3231  (1887). 
Schwalbe,  Berichte,  37,  324  (1904). 
Liebermann  and  Pleus,  Berichte,  37,  2461  (1904). 
Schwalbe,  Centralblatt  (1905),  I,  1114. 

18.  Fisher,  Lab.  Man.  of  Org.  Chem. 

19.  Gattermann,  Practical  Methods  of  Org.  Chem. 

20.  Mulliken,  "Identification  of  Pure  Organic  Compounds,"  Vol.  2. 

21.  (See  20.) 

22.  Steinkopf  and  Bauermeister,  Annalen,  403,  66  (1914). 

23.  Paal,  Berichte,  18,  2255  (1885). 
Beilstein,  III,  770. 

Meyer- Jacobson,   "Lehrbuch   der  Organischen   Chemie,"   Vol.    2, 
Part  3,  p.  145. 

24.  Zoppellari,  Gaz.  Chim.  Italiana,  24,  II,  399  (1894). 

25.  Foa,  Gaz.  Chim.  Italiana,  jp,  II,  527  (1909). 
Foa,  Centralblatt  (1910),  I,  837. 

Meyer- Jacobson,    " Lehrbuch  der  Organischen   Chemie,"   Vol.    2, 
Part  3,  p.  145. 

26.  Mulliken,  "Identification  of  Pure  Organic  Compounds,"  Vol.  2. 

27.  (See  15.) 

28.  (See  16.) 

29.  (See  17.) 

30.  (See  26.) 

31.  (See  26.) 

32.  (See  26.) 

33.  (See  15.) 

34.  (See  16.) 

35.  (See  17.) 

36.  Bender  und  Erdmann,  Chemische  Praparatenkunde,  Vol.  2,  291. 
Alfred  Deutsch,  Berichte,  12,  116  (1879). 

37.  Claisen,  Berichte,  40,  3908  (1007). 

38.  Claisen,  Berichte,  20,  657  (1887). 


VITA 

Pilar  Perez  Herrera  was  born  in  Manila,  Philippine  Islands.  She 
entered  the  University  of  the  Philippines  in  1912,  receiving  the  degrees 
of  Graduate  in  Pharmacy  in  1915  and  Bachelor  of  Science  in  1916.  From 
1916  to  1918  she  was  assistant  instructor  in  chemistry  in  the  University 
of  the  Philippines.  In  1918  she  was  granted  a  traveling  fellowship  of 
four  years  by  the  University  of  the  Philippines.  She  entered  Columbia 
University  in  the  same  year  and  in  1919  obtained  her  M.  A.  degree. 

She  is  a  member  of  Sigma  Xi,  Kappa  Mu  Sigma,  and  of  the  American 
Chemical  Society. 


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